Microbiocidal naphthenyl imidazolines

ABSTRACT

WHEREIN R is the residue of a naphthene-carboxylic acid as a microbiocidal preservative agent.   A method of preserving cosmetics by admixing with the cosmetic formulation a microbiocidally effective amount of 1-aminoethyl-2naphthenyl imidazoline, having the structure:

Adams et al.

[ MlCROBlOCIDAL NAPHTHENYL IMIDAZOLINES [75] Inventors: Phillip Adams,Murray Hill; Alfonso N. PetroccLGlen Rock, both of NJ.

[73] Assignee: Millmaster Onyx Corporation, New

York, NY.

[22] Filed: June 29, 1972 [21] Appl. No.: 267,607

Related US. Application Data [63] Continuation-in-part of Ser. No.883,641, Dec. 9,

1969, Pat. No. 3,705,027.

[52] US. Cl 424/200, 424/69, 424/70, 424/273 [51] Int. Cl. A0ln 9/22,A61k 7/00 [58] Field of Search 424/273, 69, 70, 198, 200

[56] References Cited UNITED STATES PATENTS 2,832,715 4/1958 Jezl et al424/30 3,705,027 12/1972 Adams et al 424/273 1 Jan. 21, 1975 PrimaryExaminerVincent D. Turner Attorney, Agent, or FirmArthur A. Jacobs, Esq.

[ ABSTRACT wherein R is the residue of a naphthene-carboxylic .acid as amicrobiocidal preservative agent.

5 Claims, N0 Drawings MICROBIOCIDAL NAPHTHENYL IMIDAZOLINES' II 11 II con HQNCI-hCH -N N wherein R is the residue of a naphthene-carboxylicacid.

It has been discovered that the above-naphthenyl imidazolines have ahigh order of microbiocidal effectiveness which is greatly superior toother imidazolines having different acid residues.

They are especially utilizable to preserve cosmetics so as to preventphase separation, discoloration and other effects of microbialproliferation, including that of pathogenic strains of microorganismswhich may cause serious or minor infection of the skin or mucosa.

Naphthenic acids are well-known to the art and are availablecommercially, primarily as the result of various extractive procedurescarried out in refining naturally occurring petroleums and petroleumfractions, particularly gas-oil distillates boiling in the range of400700F. Naphthenic acids are found particularly in petroleumsoriginating in the western part of the United States, especially inCalifornia; in the northern part of South America, especially Venezuela,Colombia and Aruba; in the southern part of Europe, especially Rumania,and, to a lesser extent, in crude oils originating in Louisiana, alongthe Texas gulf coast, in

Peru, Mexico, Poland, the Soviet Union and Germany.

The chemical 'nature of these naphthenic acids is more or lessill-defined, but they all have in'common the characteristic ofpossessing alicyclic nuclei. These may be five or six membered carbonatom ring systems, various condensed ring systems, and other relatedmaterials' as disclosed in Fieser, Organic Chemistry, 3rd ed. 1956,pages 97-98.

EXAMPLE 1 2,324 grams (or 9.28 mols) of Enjays Refined Naphthenic Acidhaving an acid number of 224, and 1,265 grams (or 12.07 mols) ofdiethylene triamine were charged into an agitated flask fitted withapacked fractionating column system for the purpose of separating andremoving water formed in the reaction and return ing stripped amine tothe reactor. Aquametric titration of the charged amine indicated a watercontent of 1.17%.

The mixture was agitated and heated under reduced pressure at about150C. pot temperature and at 216 mm pressure, gradually raising the pottemperature to about 200C. during a period of about 12 hours. The waterof reaction distilled along with some of the diethylene triamine,through the fractionating column, which stripped off the water andreturned the amine to the reactor. When no more water distilled, theexcess amine was distilled off at about 5 mm pressure and. 190C.

The total amount of water collected was 321 grams;

correcting for the initial water content, [7 mols of water was obtained,or 91.5% of the theoretical amount for the formation of the imidazoline.

A weighed sample was titrated potentiometrically to the first break withHCl in alcohol, indicating 87.4% activity. After reacting thenon-tertiary nitrogen with phenyl isothiocyanate, titration withperchloric acid indicated 95.2% reaction.

The product was found to be effective against aerobic bacteria at from25 to parts per million at 37C. during 4 hours.

EXAMPLE 2 The product was assayed bacteriologically by the StandardBroth Dilution Test Method. Aliquots of a solution of the aminoethylnaphthenyl imidazoline were added to appropriate broth culture mediacontained in test tubes, so that various concentrations were obtained.The tubes so prepared were inoculated with 24 hour broth cultures of thetest bacteria, or 14 day aqueous spore suspensions of the test fungi, or7 day broth cultures of the algae. Theinoculated tubes were incu batedas follows: bacteria for 72 hours at 37C.; fungi for 14 days at 28C.;algae for 7 days at 25C. Following the aforementioned incubation periodsthe tubes were examined for the presence or absence of macroscopicgrowth. The lowest concentration of test material not permittingmacroscopic growth is designated as the Minimum lnhibitory Level.

The test organisms employed were: Escherichia coli E.c.; Pseudomonasaeruginosa ps.a.; Staphylococcus aureus 8a; Streptococcus faecalis S.f.;Asprgillus niger A.n., Penicilium-expansum P.e.; and Chlorellapyrenoidosa C.p.

Table 1 Parts per million of l-aminoethyl-2-naphthenyl imidazoline AT0.5% of l-aminoethyl-2-naphthenyl imidazoline as a component of facecreams and lotions, microbial growth on storage was found to benegligible. In the case of other cosmetic preparations, such as baby 10-tions, hair-set preparations, powders,. shampoos, and the like,preservation action was excellent in the range of 0.1% to 2% by .weight.

This compound may be employed either as the free amine or as its saltsof inorganic or organic acids. Such acids may include, for example,hydrochloric, sulfuric, phosphoric, acetic, lauric, oleic, gluconic,oxalic, tartaric, citric, benzoic and substituted benzoic, paratoluenesulfonic, sulfamic, and the like.

EXAMPLE 4 Non-ionic Baby Lotion (sorbitan monooleate) Naphthenylimidazoline 0.5 Distilled Water 0.5. to make l00.0

Here, and'in the succeeding examples, naphthenyl imidazoline or moresimply, imidazoline will be understood to represent thel-aminoethyl-2-naphthenyl imidazoline of the invention. Although thefree amine is named, as readily soluble in the oily it may also beemployed in an aqueous phase as one of its salts.

The oil, lanolin, cetyl alcohol, Tween and Span were combined and mixedand heated to 60C. The water was heated to 62C and slowly added to themix with propeller agitation. The resulting emulsion was allowed to coolto room temperature under agitation. The product had a pH of about 7.0.

sorbitol beeswax derivative) Naphthenyl imidazoline 0.5 Distilled water,0.5. to make l00.0

The mineral oil, beeswax, imidazoline and the surfactants were combinedand heated under agitation to 70C; the water was heated to 72C. and thenadded slowly, with propeller agitation, to the oily phase.

The cream was allowed to cool with adequate agitation to the set-point,and poured into jars.

The pH was in the range of about 6.5 to 7.0.

EXAMPLE 6 Shampoo Component Parts by Weight Onyx Chemical Co.'s Maprofix563" 12.0

(99% active sodium lauryl sulfate) Onyx Chemical Co.'s Super Amide L 9C3.0 (methyl laurate-diethanolamine condensate 97% paste) Naphthenylimidazoline 0.5 Distilled water 0.8. to make 100.0

Heat the water to 50C. Slowly add the Maprofix while agitating, until itis completely dissolved. Add the Super Amide, previously melted and theimidazoline. Agitate until clear, while cooling.

Adjust the pH to 7.0.

EXAMPLE 7 Creme Rinse Component Parts by Weight Onyx Chemical Co.sAmmonyx 4" 7.5

(25% active) Cetyl alcohol 03 Potassium chloride 0.75 lmidazoline 0.5

Distilled water 0.5. to make 1000 EXAMPLE 8 Body Lotion Component Partsby Weight Amerchol Cholesterol Products, Inc. 5.0

Amerchol L-lO" Amerchols Acetulan" Triple-pressed stearic acid Glycerylmonostearate Propylene glycol Triethanolamine lmidazoline Distilledwater 5 Q. S. to m ke 100.0-

The first four components and the imidazoline" are combined and areheated together to C. The mixed water, propylene glycol andtriethanolamine are separately heated to 85C and added slowly to theoily phase while mixing. The agitation is continued while cooling toroom temperature.

The pH of the product is about 8.0.

The invention claimed is:

l. A method of inhibiting the growth of bacteria or fungi in creams,lotions and shampoos subject to such growth which comprises applying tosaid bacteria or fungi an amount sufficient to inhibit their growth ofthe compound 1-aminoethyl-2-naphthenyl imidazoline or a salt thereofselected from the group consisting of the hydrochloric, sulfuric,phosphoric, acetic, lauric, oleic, gluconic, oxalic, tartaric, citric,benzoic, paratoluene, sulfonic and sulfamic acid salts.

2. The method of claim 1 wherein the cosmetic is a lotion.

3. The method of claim 2 wherein the cosmetic is a cold cream.

4. The method of claim 1 wherein the cosmetic is a shampoo.

5. The method of claim 1 wherein the cosmetic is a creme rinse.

2. The method of claim 1 wherein the cosmetic is a lotion.
 3. The methodof claim 2 wherein the cosmetic is a cold cream.
 4. The method of claim1 wherein the cosmetic is a shampoo.
 5. The method of claim 1 whereinthe cosmetic is a creme rinse.